Anaesthesia, and particularly general anaesthesia, is a high risk form of treatment for a patient. The rate of metabolism of an anaesthetic in individuals varies widely, as does the level of effectiveness. Patient safety requires that they be continuously observed for signs of distress and levels of consciousness. It is also desirable, for a given individual patient, to be able to establish the level of anaesthetic effectiveness, the rate at which this is achieved and the anaesthetic dosage level required to maintain an appropriate level of unconsciousness. Patient care can therefore be optimised by minimising side effects and recovery time, and maximising anaesthetic effectiveness.
For optimised patient care, a rapid and specific analytical method is needed for measuring concentrations of anaesthetics in biological fluids, as distinct from closely related compounds. This need has led to the development of a variety of procedures for monitoring both levels of consciousness in patients and levels of anaesthetic in blood or plasma.
Patient monitoring techniques generally comprise physical monitoring of indicators such as heart rate, blood pressure and eye flicker. EEG monitoring is also feasible.
Anaesthesia monitoring generally relies on measurement of expiration gases, or more recently high performance liquid chromatography (HPLC) or ELISA for analytes in biological fluid samples.
Some twenty years ago U.S. Pat. No. 4,069,105 disclosed enzyme immunoassays for measuring levels of anaesthetics involving anilides, lidocaine being illustrative. The anaesthetics described therein were generally formulated for administration other than intravenously, with assays being carried out on samples removed from the patient.
The anaesthetic derivatives therein comprised anilide functionality drugs, linked via an annular amino substituent to antigens to produce an antigenic conjugate. In turn, the antigenic conjugate was used for the production of antibodies to the subject drug, and for use in immunoassays.
In U.S. Pat. No. 4,650,771 in 1983, the art was further developed by providing anilide derivative anaesthetics conjugated to antigens via one of the aromatic methyl substituents. Immunoassays on fluid samples were again proposed.
In 15 to 20 years which followed the publication of these U.S. patents, there have been many developments in the field of anaesthesia. Currently preferred anaesthetics are formulated for intravenous or intramuscular administration and include phenol derivative anaesthetics such as propofol. Propofol, commonly known as Diprivan is a fast acting anaesthetic commonly intravenously administered in medial anaesthesia. The existence of this preferred anaesthetic has been know for tens of years.
While this anaesthetic can be measured using HPLC methods, there are currently no methods to measure the concentration of the intravenous/intramuscular anaesthetics in patients in real-time, on-line or with easy convenience in a clinical setting. Moreover, no known antibody detection methods to these types of anaesthetics are in clinical use. As the mechanism of action of these anaesthetics are also poorly understood, the development of binding materials for these anaesthetics to enable rapid and clinically relevant detection methods using kits or off-line or in real-time biosensors would therefore fulfill a long felt want.
Other phenols are important in medicine, industry and as environmental contaminants. Improved convenient assays for these compounds are likewise desirable.
It is an object of this invention to provide new binding materials for use in detection of phenols and biosensors and/or methods which go some way to addressing the aforegoing or at least provide the public with a useful choice.